Acute promyelocytic leukemia (acute promyelocytic leukemia) - Genes PML and RARA.

Acute promyelocytic leukemia is a form of acute myelogenous leukemia, a neoplasm of bone marrow. In normal bone marrow, hematopoietic stem cells produce red blood cells carry oxygen, leukocytes that protect the body from infection and thrombocytes that are involved in blood clotting. In acute promyelocytic leukemia, immature leukocyte, called promyelocytes, accumulate in the bone marrow. Excessive accumulation of promyelocytes leads to a deficiency of red blood cells, white blood cells and thrombocytes normal in the body, which leads to many of the signs and symptoms of the disease.

People with acute promyelocytic leukemia are particularly susceptible to developing hematomas, petechiae, nosebleeds, bleeding gums, hematuria and excessive menstrual bleeding. Abnormal bleeding and bruising occur, partly due to thrombocytopenia because cancer cells release substances that cause excessive bleeding. Anemia can cause people with acute promyelocytic leukemia present paleness and tiredness. In addition, affected individuals may have frequent infections due to loss of normal white blood cells that fight infection. Also, the leukemia cells can spread to the bones and joints, causing pain in these areas. Other signs and symptoms may include fever, anorexia and weight loss. Although this disease can be diagnosed at any age, it most often diagnosed around 40 years.

This process is due to mutations in genes PML, located on the long arm of chromosome 15 (15q22) and RARA, located on the long arm of chromosome 17 (17q21). The PML gene encodes a protein that acts as a tumor suppressor. This protein is found in the PML nuclear bodies (PML-NBS). PML-NB in, the protein interacts with other proteins which are involved in growth, proliferation and apoptosis. The PML protein is able to block cell proliferation and induce apoptosis in combination with other proteins. It is believed that the structure of the PML-NBS is required to block proliferation and induction of apoptosis.

The mutation that causes acute promyelocytic leukemia involves two genes, the PML gene on chromosome 15 and RARA gene on chromosome 17. A translocation between chromosomes 15 and 17 (t (15; 17)), fused gene part PML with part of RARA gene. The protein encoded from this fused gene PML-RAR, does not locate the PML-NB, and structures do not form properly. The PML-RAR protein is unable to block cell proliferation or induce apoptosis. Furthermore, the role of RAR protein encoded from RARA gene is interrupted. Normally, this protein is involved in regulating gene transcription. Specifically, this protein helps control the transcription of certain genes involved in differentiation of white blood cells beyond the stage of promyelocytes. However, PML-RAR protein inhibit gene transcription. The PML-RAR protein allows abnormal proliferation of cells and blocks the differentiation of white blood cells in the step of promyelocytes. As a result, an excess of promyelocytes accumulate in the bone marrow and white blood cells normal blood can not be formed, resulting in acute promyelocytic leukemia.

Acute promyelocytic leukemia not inherited but arises from a translocation body cells that occurs after conception.

Tests in IVAMI: in IVAMI perform detection of mutations associated with acute promyelocytic leukemia, by complete PCR amplification of exons PML and RARA delos genes, respectively, and subsequent sequencing.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).